Rho-kinases và bệnh suy hô hấp mãn tính (COPD)
Tác giả : các Bác Sĩ Dương Quí Sĩ, T Hua-Huy, P. Dao, C. Perrotin và Giáo sư Đinh Xuân Anh-Tuấn

Bài này sẽ được trình bày tại Hội Nghị Phổi Âu Châu (European Respiratory Society) tại Berlin vào ngày 5 tháng 10 năm 2008.

Rho-kinase activity is related to pulmonary endothelial dysfunction in patients with chronic obstructive pulmonary disease (COPD)
S. Duong-Quy (1), T. Hua-Huy (1), P. Dao (1), C. Perrotin (1), A.T. Dinh-Xuan (1)
(1) : Laboratoire de Physiologie Respiratoire, UPRES-EA 2511-Hôpital Cochin & Faculté de Médecine, Université Paris Descartes
E-mail : anh-tuan.dinh-xuan@cch.aphp.fr

Introduction
Recent studies have suggested that the small monomeric G-protein, RhoA, with its downstream effectors Rho-kinase (Rock) -I and -II, play a major role in pulmonary vasoconstriction and vascular remodelling in experimental pulmonary hypertension. The aim of this study was to evaluate the the activity of RhoA/Rho-kinase in pulmonary vessels from COPD patients.
Methods
Three groups of patients, including nonsmokers (group 1), active smokers with normal lung function (group 2), and patients with COPD (group 3), underwent lung resection for carcinoma. Vascular reactivity was assessed on pulmonary arterial ring in organ bath chambers (Emka Technologies) in response to endothelium-dependent (ACh) or independent (SNP, Zaprinast) pulmonary vasodilators. Protein expressions of eNOS, Rock-I, Rock-II in pulmonary arteries and parenchymal tissues were measured by immunohistochemistry and western blot. Activity of Rho-kinase pathway (GTP-RhoA) was evaluated by immunoprecipitation technique. Data are expressed as mean +/- SD, p<0.05 was considered statistically significant.
Results
A total of twenty-four patients were studied. COPD patients had FEV1 = 59±10%. The maximal relaxation response to Ach was higher in group 1 than group 2 and group 3 (79 ± 9% vs 23 ± 19%, 21 ± 12%, respectively; p < 0.001). There were no significant differences between 3 group with regards to the degree of relaxation in response to SNP and Zaprinast (p>0.05). eNOS expression was not different between the 3 groups (2.00 ± 0.92, 2.50 ± 1.31, and 2.10 ± 0.83, respectively). Rock-I and Rock-II protein expressions were significantly higher in smokers non-COPD and COPD patients than in nonsmokers (905 ± 393, 1016 ± 599 and 1268 ± 335, 1148 ± 422 vs 233 ± 221, 464 ± 172; respectively). There was a significant difference in the percentage of GTP-RhoA/Total RhoA of smokers non-COPD and COPD patients as compared with nonsmokers (50 ± 14% and 59 ± 15% vs 15 ± 11%, p < 0.01), but there was a non significant difference between COPD patients and smokers with normal lung function (59 ± 15% vs 50 ± 14%, p > 0.05).
Conclusion
Endothelium-dependent relaxation in smokers with normal lung function and in mild to moderate COPD patients was impaired and significantly related to up-regulation of RhoA/Rho-kinase activity.
Key-words: COPD, eNOS, RhoA/Rho-kinase, endothelium-dependent relaxation

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